Reduction of Doxorubicin Cardiotoxicity by Prolonged Continuous Intravenous Infusion

Abstract

Doxorubicin (Adriamycin) was administered by continuous infusion to reduce peak plasma levels and thus lessen cardiac toxicity. Cardiotoxicity was monitored by noninvasive methods, and endomyocardial biopsy specimens were studied by electronmicroscopy. Cardiotoxicity was compared in 21 patients receiving doxorubicin intravenously over 48 or 96 hours and in 30 control patients treated by standard intravenous injection. Both groups were studied prospectively and were well matched by risk factors for doxorubicin cardiotoxicity. The median cumulative dose for those receiving continuous infusion was 600 mg/m2 body surface area (range, 360 to 1500 mg/m2) compared with 465 mg/m2 (range 290 to 680 mg/m2) in the control group (p = 0.002). Fourteen of the 30 patients in the control group showed severe morphologic changes in the biopsy specimens, precluding further doxorubicin administration, as compared with two of 21 patients receiving the drug by continuous infusion (p less than 0.02). The mean pathologic score for the infusion group, 0.9, was lower than the mean for the control group, 1.6 (p = 0.004). Antitumor activity was not compromised. Decreasing peak plasma levels of doxorubicin by continuous infusion reduces cardiotoxicity.

Activity and safety of dose‐adjusted infusional cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy with rituximab in very elderly patients with poor‐prognostic untreated diffuse large B‐cell non‐Hodgkin lymphoma

“…11 In a prospective phase II study of infusional etoposide, vincristine, and doxorubicin (EPOCH regimen) in recurrent and resistant lymphomas, no clinically significant cardiac toxicity was observed, despite that 94% of patients had previously received an anthracycline-containing regimen. 12 However, pharmacokinetic analyses of long-term continuousinfusion doxorubicin have shown, particularly for older patients, significant interpatient variations in steady-state plasma concentrations and have suggested an individual patient dose adjustment based on hematopoietic nadir.…”

Congestive heart failure in patients treated with doxorubicin

“…1 Legha et al studied continuousinfusion doxorubicin and found that endomyocardial biopsy changes were significantly less severe than in patients receiving bolus infusion. 12 Reduction of the cardiotoxic profile of the anthracycline itself continues to be of interest. Epirubicin reportedly had lower cardiotoxicity compared with doxorubicin on the basis of a mg/m 2 cumulative dose.…”

Delivery of adjuvant sequential dose-dense FEC–Doc to patients with breast cancer is feasible, but dose reductions and toxicity are dependent on treatment sequence

“…Densification of FEC 100 from 3-weekly to 2-weekly with G-CSF support has, however, been found unfeasible as a result of high toxicity, including pericardial effusion, pneumonitis and frequent hospitalisations [19,20]. Decreasing peak plasma levels of doxorubicin by continuous infusion has also been shown to reduce cardiotoxicity [21]. Dose densification of Doc therapy is feasible, as demonstrated in a study of biweekly doxorubicin 50 mg/m 2 and Doc 75 mg/m 2 [22].…”